术后腹腔粘连形成机制及间充质干细胞外泌体的治疗前景  

Mechanism of postoperative abdominal adhesion formation and therapeutic prospect of mesenchymal stem cell exosomes

作　　者：张兴洲[1] 魏明 董国强 杜为 罗依雯 张楠[1] Zhang Xingzhou;Wei Ming;Dong Guoqiang;Du Wei;Luo Yiwen;Zhang Nan(Department of Gastrointestinal Surgery,Tianjin Nankai Hospital,Tianjin 300100,China;Department of Obstetrics and Gynecology,Tianjin Nankai Hospital,Tianjin 300100,China;Tianjin Key Laboratory of Blood Cell Therapy Technology,Tianjin 300100,China;Clinical College of Tianjin Medical University,Tianjin 300270,China)

机构地区：[1]天津市南开医院胃肠外科,天津市300100 [2]天津市南开医院妇产科,天津市300100 [3]天津市血液细胞治疗技术企业重点实验室,天津市300100 [4]天津医科大学临床学院,天津市300270

出　　处：《中国组织工程研究》2025年第1期147-155,共9页Chinese Journal of Tissue Engineering Research

基　　金：天津市卫生健康委天津市中医药管理局中医中西医结合科研课题(2023167),项目负责人:张兴洲。

摘　　要：背景:术后腹腔粘连的形成是一个复杂的过程,预防术后粘连是临床上亟待解决的问题。目的:旨在从细胞及分子水平分析粘连的发生机制,为间充质干细胞外泌体预防和治疗粘连提供理论依据。方法:以“腹腔粘连,盆腔粘连,术后粘连,上皮间充质转化,间充质干细胞,干细胞外泌体,间充质干细胞外泌体”为中文检索词,以“Abdominal adhesion,pelvic adhesion,postoperative adhesion,epithelial mesenchymal transformation,mesenchymal stem cell,stem cell exosomes,mesenchymal stem cell exosomes”为英文检索词,检索PubMed、中国知网和中国生物医学文献数据库,筛选各数据库建库至2023年8月发表的术后腹腔粘连及间充质干细胞外泌体干预研究的相关文章,并进行系统的整理分析,最终纳入54篇文献进行综述。结果与结论:(1)任何腹膜炎症、机械损伤、组织缺血和异物植入等病理因素均可引起腹膜表面的损伤,引起术后腹腔粘连;腹腔粘连的形成过程包括腹膜间皮细胞修复、炎性反应、纤溶系统及凝血途径等过程的相互作用,涉及多种细胞因子及信号通路,包括Wnt/β-catenin通路能诱导纤维化和血管生成,并与转化生长因子β/Smads信号通路相互协同,能刺激成纤维细胞增殖,引起腹膜纤维化;同时,核转录因子kB信号通路上调细胞炎症因子的表达,促进成纤维细胞增生,组织纤维化的过程中发挥关键作用。(2)干细胞的旁分泌功能是目前以再生医学为基础的分子干预腹腔粘连的重要方向,可以参与作用于腹腔粘连中的多种复杂细胞因子及信号通路。(3)相对于传统治疗腹腔粘连的方法,间充质干细胞外泌体具有生物活性、使用安全、无需特殊培养和扩增、更低的免疫原性及较长的稳定性等优势,能通过多种途径引导一种正常的修复和愈合。(4)间充质干细胞外泌体在以往研究中均被证明可以参与调节粘连形成的上述各过程,BACKGROUND:The formation of postoperative abdominal adhesions is a complicated process,and the prevention of postoperative adhesions is an urgent problem in clinic.OBJECTIVE:To analyze the mechanism of adhesion at cellular and molecular levels,and to provide theoretical basis for the prevention and treatment of adhesion by mesenchymal stem cell exosomes.METHODS:“Abdominal adhesion,pelvic adhesion,postoperative adhesion,epithelial mesenchymal transformation,mesenchymal stem cells,stem cell exosomes,mesenchymal stem cell exosomes”were selected as Chinese and English search terms.We searched PubMed,CNKI,and Chinese biomedical literature and screened relevant articles on postoperative abdominal adhesion and mesenchymal stem cell exosomal intervention published from inception to August 2023.After systematic analysis,54 articles were finally included for the review.RESULTS AND CONCLUSION:(1)Any pathological factors such as peritoneal inflammation,mechanical injury,tissue ischemia,and foreign body implantation cause peritoneal surface injury,resulting in postoperative abdominal adhesion.The formation process of adhesion includes the interaction of peritoneal mesothelial cell repair,inflammatory response,fibrinolytic system,coagulation pathway and other processes,involving a variety of cytokines and signaling pathways.Wnt/β-catenin pathway can induce fibrosis and angiogenesis,and cooperate with transforming growth factor-β/Smads signaling pathway to stimulate fibroblast proliferation and cause peritoneal fibrosis.Meanwhile,nuclear factor-κB signaling pathway up-regulates the expression of cellular inflammatory factors,promotes fibroblast proliferation,and plays a key role in the process of tissue fibrosis.(2)The paracrine function of stem cells is an important direction of molecular intervention in abdominal adhesions based on regenerative medicine.It can participate in a variety of complex cytokines and signaling pathways involved in abdominal adhesions.(3)Compared with traditional methods for treating abdominal

关 键 词：术后腹腔粘连 上皮间质转化 炎症反应 纤溶系统 间充质干细胞外泌体 肿瘤坏死因子α 白细胞介素 生长因子 转化生长因子β/Smads信号通路 Wnt/β-catenin 核转录因子kB信号通路 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R605